Podocytes are the visceral epithelial cells of the kidney glomerulus. They have elaborate long, regularly spaced, interdigitated foot processes that completely enwrap the glomerular capillaries. Interdigitating podocyte foot processes form an ˜40-nm-wide filtration slit occupied by a continuous membrane-like structure called the slit diaphragm.
Podocytes are highly differentiated cells with a crucial role in the glomerular filtration barrier. When podocytes are injured, the intercellular junctions and cytoskeletal structure of the foot processes are altered and the cell takes on an “effaced” phenotype. Typical slit diaphragm structures disappear and proteinuria develops.
Proteinuria describes a condition in which urine contains an abnormal amount of protein. Proteinuria can result from inflammatory, metabolic, immunologic or genetic causes. Proteinuric diseases are either primary or secondary and can occur during systemic diseases, such as hypertension, diabetes, systemic lupus erythematosus (SLE). Examples of renal glomerular diseases are IgA nephropathy, Focal segmental glomerulosclerosis (FSGS), Membranous nephropathy and Minimal change disease (MCD), Goodpasture's syndrome, Hereditary Nephritis-Alport Syndrome, Infection-related Glomerular Disease (Acute post-streptococcal glomerulonephritis (PSGN), Bacterial endocarditis, HIV), etc.
In most cases, primary glomerulonephritis stands for a disease of still unknown etiology, meaning that there remains an imperious need for improved methods for diagnosing and treating these diseases.
The properties and role of different proteins in podocytes is poorly understood. It was previously observed that glomerular podocytes possess Rab3A, a GTPase restricted to cell types capable of highly regulated exocytosis. However, to date, the role of Rab3A in disease has not been elucidated.